1. Eligible studies
A total of 123 studies were retrieved in this study, and 62 studies were obtained after excluding the duplicate articles. Through further reading the literature titles and reading abstracts, and checking against the inclusion criteria and exclusion criteria, finally, 13 reports 4–6, 8–13, 15–18 were included in the present research, of which 11studies were randomized controlled experiments, 2 studies were single-arm experiments, and the patients studied were mainly from Hubei and Anhui provinces in mainland China. The test group was given Lianhua-Qingwen mainly combined with Western medicine treatment, and the control group was treated with conventional Western medicine treatment, with a total of 1,182 cases of COVID-19; the intervention time range was 5–20 days. The basic characteristics and patient information of the included literature are shown in Table 1.
Table 1
Characteristics of the 13 studies included in the meta-analysis
First author
|
Type of study
|
Location of study
|
N
|
Age
|
Samples(male)
|
Treatment
|
Duration (d)
|
Total
|
Intervention
|
Control
|
Intervention
|
Control
|
Intervention
|
Control
|
Intervention
|
Control
|
|
Kaitao Yao13
|
Observational
|
Hubei
|
42
|
21
|
21
|
57.1 ± 14.0
|
62.4 ± 12.3
|
16 (76. 2%)
|
12 (57.1%)
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
Conventional western medicine treatment
|
19
|
Dezhong Cheng10
|
Observational
|
Hubei
|
54
|
54
|
-
|
60.1 ± 16.98
|
-
|
29 (53.7% )
|
-
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
Conventional western medicine treatment
|
8.0 ± 4. 10
|
Ruibing Lv15
|
Observational
|
Hubei
|
101
|
63
|
38
|
59.12 ± 16.56
|
60.20 ± 17.01
|
28 (44.4%)
|
18 (47.4%)
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
Conventional western medicine treatment
|
10
|
Ping Yu6
|
Observational
|
Hubei
|
295
|
147
|
148
|
48.27 ± 9.56
|
47.25 ± 8.67
|
82 (56%)
|
89 (60%)
|
Lianhua Qingwen, Arbidol combined with conventional western medicine treatment ,6 g / time ,3 times / day
|
Conventional western medicine treatment
|
7
|
Jia Shi12
|
Observational
|
Shanghai
|
67
|
49
|
18
|
47.94 ± 14.46
|
46.72 ± 17.40
|
26 ( 38.81%)
|
10( 14.93%)
|
Shufeng Jiedu Capsule, Lianhua Qingwen Granule, etc
|
Conventional western medicine treatment
|
5–6
|
Lili Liu4
|
Observational
|
Hubei
|
32
|
18
|
14
|
-
|
-
|
-
|
-
|
Lianhua Qingwen, combined with Arbidol
|
Lianhua Qingwen,
|
20
|
Dezhong Cheng9
|
Observational
|
Hubei
|
102
|
51
|
51
|
55.5 ± 12.3
|
55.8 ± 11.6
|
26 (51%)
|
27 (52.9%)
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
Conventional western medicine treatment
|
7
|
Ke Hu11
|
RCT
|
nine provinces throughout mainland China
|
284
|
142
|
142
|
50.4 ± 15.2
|
51.8 ± 14.8
|
79 (55.6%)
|
71 (50%)
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
Conventional western medicine treatment
|
14
|
Wenguang Xia16
|
Observational
|
Hubei
|
52
|
34
|
18
|
54. 18 ± 13. 08
|
53. 67 ± 12. 70
|
17 ( 50. 0%)
|
6 ( 33. 3%)
|
Traditional Chinese Medicine Decoction, Traditional Chinese Medicine Injection
|
Antiviral drugs (Abidor, Ribavirin ,α- interferon, Lopinavir/litonavir, oseltamivir), anti-infective drugs (moxifloxacin, levofloxacin, azithromycin, cephalosporins and penicillin), adjuvant drugs (gamma globulin, methylprednisolone)
|
20
|
Shengzao Wang26
|
Observational
|
Anhui
|
60
|
30
|
30
|
-
|
-
|
-
|
-
|
Lianhua Qingwen 4 tablets / times 3 times / day ;α- interferon :500 U,2 times / day; Lopinavir / ritonavir :2 tablets / times 2 times / r day
|
Lianhua Qingwen 4 tablets / times 3 times / day ;α- interferon :500 U,2 times / day;
|
7–10
|
Facai Wang27
|
Observational
|
Anhui
|
55
|
55
|
-
|
-
|
-
|
-
|
-
|
Lianhua Qingwen Granule combined with conventional western medicine treatment ,1 bag / time ,3 times / day
|
-
|
7
|
Jiangjian Chen18
|
Observational
|
Guizhou
|
70
|
35
|
35
|
44.75 ± 4.92
|
45.21 ± 4.68
|
18 (51.4%)
|
20(57.1%)
|
Lianhua Qingwen, Granule combined with conventional western medicine treatment ,1.4 g / time ,2 times / day
|
Arbidol combined with conventional western medicine treatment
|
15
|
Fei Fang17
|
Observational
|
Hubei
|
83
|
42
|
41
|
4.8 ± 3.7
|
3.9 ± 3.2
|
18 (42.9%)
|
16 (39.1%)
|
Lianhua Qingwen Granule combined with conventional western medicine treatment
|
Conventional western medicine treatment
|
5
|
2. Overall improvement rate
Five studies report on the overall improvement rate, including 811subjects (405 patients were in the group of treatment using Lianhua-Qingwen and Western medicine, and 406 patients treated with only conventional Western medicine). The data showed that the therapy using Lianhua-Qingwen combined with Western medicine treatment improved the effectiveness of recovery of the patients with novel coronavirus by 18%, and the effective combined RR value was 1.18 (95% CI: 1.09, 1.21; I2 = 37%, Fig. 2).
3. Chest CT imaging analysis
The rate of chest CT showing recovery was detected in 6 studies including 870 subjects (458 patients were in the group of taking Lianhua-Qingwen combined with Western medicine, and 412 patients were in the group taking conventional Western medicine). The data showed that Lianhua-Qingwen combined with Western medicine treatment showed a better chest CT result in patients with novel coronavirus. The RR value of CT image improvement rate was 1.12 (95% CI: 1.03, 1.23; I2 = 38%, Fig. 3).
4. Disappearance rate of main symptoms
The main symptoms of patients with novel coronavirus pneumonia include fever, fatigue, and cough. We separately counted the effects of the two treatment methods on the disappearance rate of the main symptoms of fever, fatigue and cough, respectively.
Fever: 7 studies reported the fever disappearance rate, of which 5 studies adopted two-arm experiments and 2 studies adopted single-arm experiments, including 528 subjects (373 were in the group treated with Lianhua-Qingwen combined with Western medicine, and 155 were in the group receiving only conventional Western medicine treatment). The results of the two-arm studies were (RR = 1.43 (95% CI: 1.24, 1.65; I2 = 0%); Fig. 4a1]; the single-arm studies results were (RD = 0.90 (95% CI: 0.73, 1.07; I2 = 86 % ); Fig. 4a2).These results suggest that the combination of Lianhua-Qingwen and Western medicine more effectively improved the symptom of fever in patients with COVID-19 than the method of prescribing only Western medicines for the disease.
Fatigue: 5 studies reported the disappearance rate of fatigue, of which 3 studies used two-arm experiments, 2 studies used single-arm experiments, including a total of 269 subjects (192 patients received Lianhua-Qingwen combined with Western medicine, and 77 patients taking only conventional Western medicines). The results of the two-arm studies were (RR = 1.51 (95% CI: 1.15, 2.03; I2 = 0% ); Fig. 4b1); the results of single-arm studies were (RD = 0.80 (95% CI: 0.70, 0.90; I2 = 0 % ); Fig. 4b2).These results suggest that Lianhua-Qingwen combined with Western medicine treatment better improved the symptom of fatigue in patients with COVID-19 than the approach of using only Western medicines for the disease.
Cough: There were 6 studies on the cough disappearance rate, of which 4 studies presented were of two-arm experiments, and 2 studies carried out single-arm experiments, including a total of 379 subjects (253 patients receiving the integrated approach, and 126 taking only conventional Western medicines). The results of the two-arm study were (RR = 1.97 (95% CI: 1.45, 2.68; I2 = 0% ); Fig. 4c1); the single-arm study results were (RD = 0.74 (95% CI: 0.64, 0.84; I2 = 0 %); Fig. 4c2). They jointly illustrate that treatment with Lianhua-Qingwen combined with Western medicine better improved symptom of cough in patients with COVID-19.
5. Duration of fever
There were 3 studies on the duration of fever, including 155 subjects (91 patients were on treatment with both Chinese and Western medicine, and 64 were taking only conventional Western medicine). The data showed that treatment with Lianhua-Qingwen combined with Western medicine improved the symptom fever with shorter recovery time in patients with novel coronavirus. The recovery time was shortened by 1.33 days on average, (MD=-1.33, (95% CI: -1.92, -0.73; I2 = 5%, Fig. 5)
6). The rate of progressing to severe cases
There were 7 studies on the rate of progressing to severe cases, including 936 subjects (490 cases were treated with both Chinese and Western medicine, and 446 were treated with only conventional Western medicine). The data suggest that the therapy using Lianhua-Qingwen combined with Western medicine reduced the rate of cases that progressed from mild to severe level when compared with the treatment approach by Western medicine alone (RR = 0.50 (95% CI: 0.35, 0.73; I2 = 0%); Fig. 6)
7. Adverse reactions
Of the 13 studies included in our study, 11 studies reported treatment with Lianhua-Qingwen combined with Western medicine. Compared with the treatment by conventional Western medicine, no serious drug-related adverse reactions were seen in the group receiving Lianhua-Qingwen combined with Western medicine. Studies from 15 showed that in the group of conventional Western medicine, 38 cases complained of nausea, 5 cases of vomiting, and 3 cases of loss of appetite, the incidence of adverse reactions was 21.05%. However, in the group of Lianhua-Qingwen treatment with 63 patients, two cases complained of diarrhea, 1 case of loss of appetite, and the incidence of adverse reactions was only 4.76%, and the adverse reactions were improved in both groups after drug withdrawal. The research by Hu et al11. showed that the two groups of treatment showed abnormal liver function, renal dysfunction, headache, nausea, vomiting, diarrhea, loss of appetite and other adverse reactions, but there was no significant difference between the two groups4. Our analysis of the data also suggested that there was no significant difference in adverse reactions between the two groups: treatment with Lianhua-Qingwen combined with Western medicine vs. treatment with Western medicine treatment alone: (RR = 0.51 (95% CI: 0.14, 1.82; I2 = 76%); Fig. 7).